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In a similar vein to the developer's previous games, Amnesia is an exploration-based adventure game played from a first-person perspective. The game retains the physical object interaction used in the Penumbra series, allowing for advanced physics based puzzles and interactions such as opening doors and fixing machinery.[5]

Amnesia does not give the player access to weapons, giving them no defense against the gruesome creatures that wander Brennenburg Castle. As such, the player must use their wits to escape and hide from the monsters until they lose interest in finding the player. However, monsters are very capable of tearing down doors in their path and kicking obstacles out of the way. Players can also choose to hide in the shadows at the cost of slowly losing their sanity. Another thing the player can do is barricade doors with rocks, chairs, and other obstacles. But the monsters do move very quickly when alerted, so the player has to be quick.

Separate from the player's health bar is an indication of the character's sanity. Being in darkness too long, witnessing unsettling events, or staring at the monsters for too long will reduce the character's sanity. As the sanity level decreases, visual and auditory hallucinations start to occur and the player is noticed by monsters more easily. Using tinderboxes to light candles and other light sources, as well as a lantern found near the beginning of the game, the player can stop their sanity from draining. However, the number of tinderboxes is limited, and the lantern cannot be used when the oil is depleted. This forces the player to find a balance between the amount of time they spend in light and shadow. Sanity is restored to full once the player completes an objective or progresses the game's story. It may also be restored by staying in the shadows until the player character passes out, but this makes him extremely vulnerable to any nearby monsters.